title: Axonally derived neuregulin-1 is required for remyelination and regeneration after nerve injury in adulthood.
abstract: Neuregulin-1 (NRG1) plays a crucial role in axoglial signaling during the development of the peripheral nervous system, but its importance in adulthood after peripheral nerve injury remains unclear. We used single-neuron labeling with inducible Cre-mediated knock-out animals, which enabled visualization of a subset of adult myelinated sensory and motoneurons neurons in which Nrg1 was inducibly mutated by tamoxifen treatment. In uninjured mice, NRG1-deficient axons and the associated myelin sheath were normal, and the neuromuscular junction demonstrated normal apposition of presynaptic and postsynaptic components. After sciatic nerve crush, NRG1 ablation resulted in severe defects in remyelination: axons were either hypomyelinated or had no myelin sheath. NRG1-deficient axons were also found to regenerate at a slower rate. After nerve injury, the neuromuscular junction was reinnervated, but excess terminal sprouting was observed. Juxtacrine Neuregulin-1 signaling is therefore dispensable for maintenance of the myelin sheath in adult animals but has a key role in reparative processes after nerve injury.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, United Kingdom.
authors.forename: Florence R
authors.initials: FR
authors.lastname: Fricker
authors.forename: Natalia
authors.initials: N
authors.lastname: Lago
authors.forename: Sharmili
authors.initials: S
authors.lastname: Balarajah
authors.forename: Christoforos
authors.initials: C
authors.lastname: Tsantoulas
authors.forename: Shamil
authors.initials: S
authors.lastname: Tanna
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.forename: Samaher K
authors.initials: SK
authors.lastname: Fageiry
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkins
authors.forename: Alistair N
authors.initials: AN
authors.lastname: Garratt
authors.forename: Carmen
authors.initials: C
authors.lastname: Birchmeier
authors.forename: David L H
authors.initials: DL
authors.lastname: Bennett
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D020890:Neuregulin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse